CA2643744A1 - Cancer imaging and treatment - Google Patents
Cancer imaging and treatment Download PDFInfo
- Publication number
- CA2643744A1 CA2643744A1 CA002643744A CA2643744A CA2643744A1 CA 2643744 A1 CA2643744 A1 CA 2643744A1 CA 002643744 A CA002643744 A CA 002643744A CA 2643744 A CA2643744 A CA 2643744A CA 2643744 A1 CA2643744 A1 CA 2643744A1
- Authority
- CA
- Canada
- Prior art keywords
- arg
- tyr
- orn
- nal
- gly
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
- 206010028980 Neoplasm Diseases 0.000 title claims 6
- 238000003384 imaging method Methods 0.000 title claims 3
- 201000011510 cancer Diseases 0.000 title 1
- OUYCCCASQSFEME-MRVPVSSYSA-N D-tyrosine Chemical compound OC(=O)[C@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-MRVPVSSYSA-N 0.000 claims abstract 71
- 150000001875 compounds Chemical class 0.000 claims abstract 59
- 239000003446 ligand Substances 0.000 claims abstract 25
- 125000004122 cyclic group Chemical group 0.000 claims abstract 24
- 235000001014 amino acid Nutrition 0.000 claims abstract 19
- 150000001413 amino acids Chemical class 0.000 claims abstract 19
- 108010038807 Oligopeptides Proteins 0.000 claims abstract 17
- 102000015636 Oligopeptides Human genes 0.000 claims abstract 17
- 108010061299 CXCR4 Receptors Proteins 0.000 claims abstract 6
- 102000012000 CXCR4 Receptors Human genes 0.000 claims abstract 6
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 claims abstract 6
- 150000002148 esters Chemical class 0.000 claims abstract 6
- 150000003839 salts Chemical class 0.000 claims abstract 6
- PECYZEOJVXMISF-UHFFFAOYSA-N 3-aminoalanine Chemical compound [NH3+]CC(N)C([O-])=O PECYZEOJVXMISF-UHFFFAOYSA-N 0.000 claims abstract 5
- 102100031650 C-X-C chemokine receptor type 4 Human genes 0.000 claims abstract 5
- 101000922348 Homo sapiens C-X-C chemokine receptor type 4 Proteins 0.000 claims abstract 5
- 125000003118 aryl group Chemical group 0.000 claims abstract 5
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 claims abstract 5
- JPZXHKDZASGCLU-LBPRGKRZSA-N β-(2-naphthyl)-alanine Chemical compound C1=CC=CC2=CC(C[C@H](N)C(O)=O)=CC=C21 JPZXHKDZASGCLU-LBPRGKRZSA-N 0.000 claims abstract 4
- 238000002059 diagnostic imaging Methods 0.000 claims abstract 2
- 238000000034 method Methods 0.000 claims 16
- AHLPHDHHMVZTML-SCSAIBSYSA-N D-Ornithine Chemical compound NCCC[C@@H](N)C(O)=O AHLPHDHHMVZTML-SCSAIBSYSA-N 0.000 claims 12
- 108010068380 arginylarginine Proteins 0.000 claims 11
- -1 1-naphthylmethyl Chemical group 0.000 claims 10
- 230000001613 neoplastic effect Effects 0.000 claims 6
- 230000009826 neoplastic cell growth Effects 0.000 claims 5
- BLCJBICVQSYOIF-UHFFFAOYSA-N 2,2-diaminobutanoic acid Chemical compound CCC(N)(N)C(O)=O BLCJBICVQSYOIF-UHFFFAOYSA-N 0.000 claims 4
- OMLWNBVRVJYMBQ-YUMQZZPRSA-N Arg-Arg Chemical compound NC(N)=NCCC[C@H](N)C(=O)N[C@@H](CCCN=C(N)N)C(O)=O OMLWNBVRVJYMBQ-YUMQZZPRSA-N 0.000 claims 4
- 125000002059 L-arginyl group Chemical group O=C([*])[C@](N([H])[H])([H])C([H])([H])C([H])([H])C([H])([H])N([H])C(=N[H])N([H])[H] 0.000 claims 4
- 239000003795 chemical substances by application Substances 0.000 claims 4
- 238000010668 complexation reaction Methods 0.000 claims 4
- MBXBICVKLVYNKD-XFTNXAEASA-N Cyclo[3-(2-naphthalenyl)-l-alanylglycyl-d-tyrosyl-l-arginyl-l-arginyl] Chemical compound C([C@@H]1C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@H](C(N[C@@H](CC=2C=C3C=CC=CC3=CC=2)C(=O)NCC(=O)N1)=O)CCCN=C(N)N)C1=CC=C(O)C=C1 MBXBICVKLVYNKD-XFTNXAEASA-N 0.000 claims 3
- 230000015572 biosynthetic process Effects 0.000 claims 3
- 231100000433 cytotoxic Toxicity 0.000 claims 3
- 230000001472 cytotoxic effect Effects 0.000 claims 3
- 230000001394 metastastic effect Effects 0.000 claims 3
- 206010061289 metastatic neoplasm Diseases 0.000 claims 3
- 238000003786 synthesis reaction Methods 0.000 claims 3
- OECHUGCITYQGCY-YUMQZZPRSA-N (2s)-5-amino-2-[[(2s)-2,5-diaminopentanoyl]amino]pentanoic acid Chemical group NCCC[C@H](N)C(=O)N[C@H](C(O)=O)CCCN OECHUGCITYQGCY-YUMQZZPRSA-N 0.000 claims 2
- 206010006187 Breast cancer Diseases 0.000 claims 2
- 208000026310 Breast neoplasm Diseases 0.000 claims 2
- 206010060862 Prostate cancer Diseases 0.000 claims 2
- 208000000236 Prostatic Neoplasms Diseases 0.000 claims 2
- 125000002252 acyl group Chemical group 0.000 claims 2
- 210000000481 breast Anatomy 0.000 claims 2
- 238000001514 detection method Methods 0.000 claims 2
- 239000003814 drug Substances 0.000 claims 2
- AHLPHDHHMVZTML-BYPYZUCNSA-N ornithyl group Chemical group N[C@@H](CCCN)C(=O)O AHLPHDHHMVZTML-BYPYZUCNSA-N 0.000 claims 2
- 238000002360 preparation method Methods 0.000 claims 2
- MJOGHHIGMBYMHS-REOHCLBHSA-N (2s)-2-(aminooxyamino)-3-hydroxypropanoic acid Chemical compound NON[C@@H](CO)C(O)=O MJOGHHIGMBYMHS-REOHCLBHSA-N 0.000 claims 1
- UOQXIWFBQSVDPP-UHFFFAOYSA-N 4-fluorobenzaldehyde Chemical compound FC1=CC=C(C=O)C=C1 UOQXIWFBQSVDPP-UHFFFAOYSA-N 0.000 claims 1
- 125000002849 D-tyrosine group Chemical group [H]N([H])[C@@]([H])(C(=O)[*])C([H])([H])C1=C([H])C([H])=C(O[H])C([H])=C1[H] 0.000 claims 1
- AHLPHDHHMVZTML-UHFFFAOYSA-N Orn-delta-NH2 Natural products NCCCC(N)C(O)=O AHLPHDHHMVZTML-UHFFFAOYSA-N 0.000 claims 1
- UTJLXEIPEHZYQJ-UHFFFAOYSA-N Ornithine Natural products OC(=O)C(C)CCCN UTJLXEIPEHZYQJ-UHFFFAOYSA-N 0.000 claims 1
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims 1
- 125000003368 amide group Chemical group 0.000 claims 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims 1
- 125000001153 fluoro group Chemical group F* 0.000 claims 1
- 125000000524 functional group Chemical group 0.000 claims 1
- 125000005842 heteroatom Chemical group 0.000 claims 1
- 238000000338 in vitro Methods 0.000 claims 1
- 238000001727 in vivo Methods 0.000 claims 1
- 238000002347 injection Methods 0.000 claims 1
- 239000007924 injection Substances 0.000 claims 1
- 239000000203 mixture Substances 0.000 claims 1
- 230000000269 nucleophilic effect Effects 0.000 claims 1
- 229960003104 ornithine Drugs 0.000 claims 1
- 150000002923 oximes Chemical class 0.000 claims 1
- 239000008194 pharmaceutical composition Substances 0.000 claims 1
- 239000000546 pharmaceutical excipient Substances 0.000 claims 1
- 108010018625 phenylalanylarginine Proteins 0.000 claims 1
- 238000002603 single-photon emission computed tomography Methods 0.000 claims 1
- 125000006850 spacer group Chemical group 0.000 claims 1
- 125000001424 substituent group Chemical group 0.000 claims 1
- 238000002560 therapeutic procedure Methods 0.000 claims 1
- 210000001519 tissue Anatomy 0.000 claims 1
- 239000002253 acid Substances 0.000 abstract 2
- 230000001225 therapeutic effect Effects 0.000 abstract 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
- C07K7/64—Cyclic peptides containing only normal peptide links
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
- A61K38/12—Cyclic peptides, e.g. bacitracins; Polymyxins; Gramicidins S, C; Tyrocidins A, B or C
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K51/00—Preparations containing radioactive substances for use in therapy or testing in vivo
- A61K51/02—Preparations containing radioactive substances for use in therapy or testing in vivo characterised by the carrier, i.e. characterised by the agent or material covalently linked or complexing the radioactive nucleus
- A61K51/04—Organic compounds
- A61K51/08—Peptides, e.g. proteins, carriers being peptides, polyamino acids, proteins
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K51/00—Preparations containing radioactive substances for use in therapy or testing in vivo
- A61K51/02—Preparations containing radioactive substances for use in therapy or testing in vivo characterised by the carrier, i.e. characterised by the agent or material covalently linked or complexing the radioactive nucleus
- A61K51/04—Organic compounds
- A61K51/08—Peptides, e.g. proteins, carriers being peptides, polyamino acids, proteins
- A61K51/088—Peptides, e.g. proteins, carriers being peptides, polyamino acids, proteins conjugates with carriers being peptides, polyamino acids or proteins
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/04—Antineoplastic agents specific for metastasis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/574—Immunoassay; Biospecific binding assay; Materials therefor for cancer
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Organic Chemistry (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Molecular Biology (AREA)
- Engineering & Computer Science (AREA)
- Biochemistry (AREA)
- Physics & Mathematics (AREA)
- Epidemiology (AREA)
- Immunology (AREA)
- Biophysics (AREA)
- Optics & Photonics (AREA)
- Genetics & Genomics (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Oncology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Urology & Nephrology (AREA)
- Hematology (AREA)
- Biomedical Technology (AREA)
- Cell Biology (AREA)
- Biotechnology (AREA)
- Hospice & Palliative Care (AREA)
- Microbiology (AREA)
- Gastroenterology & Hepatology (AREA)
- Food Science & Technology (AREA)
- Analytical Chemistry (AREA)
- General Physics & Mathematics (AREA)
- Pathology (AREA)
- Peptides Or Proteins (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
Abstract
A compound, or a pharmaceutically acceptable salt or ester thereof, comprises a ligand for the chemokine receptor CXCR4 and a detectable label, the ligand having a binding affinity for the CXCR4 receptor, measured as IC50 in the presence of 125I-CPCR4, of 25OnM or lower, wherein the ligand comprises a cyclic oligopeptide moiety having the motif B-Arg or B- (Me)Arg within the cyclic moiety, and wherein B is a basic amino acid; a derivative thereof, or phenylalanine, provided that the motif is B-Arg when B is a N.alpha.-methyl derivative of a basic amino acid. In preferred embodiments, the cyclic oligopeptide moiety has the sequence: cyclo[D-Tyr/(Me)D-Tyr - B - Arg/(Me)Arg - Z - (Ala)n - X] wherein: B is as defined above; Z is an amino acid containing an aromatic group in its side chain; n is 1 or 0, provided that n is 1 only when the preceding four amino acids in the cyclic moiety sequence are D-Tyr/(Me)D-Tyr-Arg-Arg-Nal, NaI being L-3-(2-naphthyl)alanine; and X is selected from GIy, (Me)GIy, Ala, Dap (diaminopropionic acid), Dap(FP) ((N- fluoropropionyl)-diaminopropionic acid), Dab (diaminobutyiic acid), Dab(FP) ((N- fluoropropionyl)-diaminobutyric acid), Dab(FB) ((N-fluorobenzoyl)-diaminobutyric acid) and Dap(FB) ((N-fluorobenzoyl)-diaminopiOpionic acid). The compounds may be useful for diagnostic imaging and/or therapeutic purposes.
Claims (54)
1. A compound, or a pharmaceutically acceptable salt or ester thereof, comprising a ligand for the chemokine receptor CXCR4 and a detectable label, the ligand having a binding affinity for the CXCR4 receptor, measured as IC50 in the presence of CPCR4, of 250nM or lower, wherein the ligand comprises a cyclic oligopeptide moiety having the motif B-Arg or B-(Me)Arg within the cyclic moiety, and wherein B
is a basic amino acid, a derivative thereof, or phenylalanine, provided that the motif is B-Arg when B is a N .alpha.-methyl derivative of a basic amino acid.
is a basic amino acid, a derivative thereof, or phenylalanine, provided that the motif is B-Arg when B is a N .alpha.-methyl derivative of a basic amino acid.
2. A compound according to claim 1, wherein the cyclic oligopeptide moiety has the sequence:
cyclo[D-Tyr/(Me)D-Tyr - B - Arg/(Me)Arg - Z -(Ala)n - X]
wherein:
B is as defined in claim 1;
Z is an amino acid containing an aromatic group in its side chain;
n is 1 or 0, provided that n is 1 only when the preceding four amino acids in the cyclic moiety sequence are D-Tyr/(Me)D-Tyr-Arg-Arg-Nal, Nal being L-3-(2-naphthyl)alanine; and X is selected from Gly, (Me)Gly, Ala, Dap (diaminopropionic acid), Dap(FP) ((N-fluoropropionyl)-diaminopropionic acid), Dab (diaminobutyric acid), Dab(FP) ((N-fluoropropionyl)-diaminobutyric acid), Dab(FB) ((N-fluorobenzoyl)-diaminobutyric acid) and Dap(FB) ((N-fluorobenzoyl)-diaminopropionic acid).
cyclo[D-Tyr/(Me)D-Tyr - B - Arg/(Me)Arg - Z -(Ala)n - X]
wherein:
B is as defined in claim 1;
Z is an amino acid containing an aromatic group in its side chain;
n is 1 or 0, provided that n is 1 only when the preceding four amino acids in the cyclic moiety sequence are D-Tyr/(Me)D-Tyr-Arg-Arg-Nal, Nal being L-3-(2-naphthyl)alanine; and X is selected from Gly, (Me)Gly, Ala, Dap (diaminopropionic acid), Dap(FP) ((N-fluoropropionyl)-diaminopropionic acid), Dab (diaminobutyric acid), Dab(FP) ((N-fluoropropionyl)-diaminobutyric acid), Dab(FB) ((N-fluorobenzoyl)-diaminobutyric acid) and Dap(FB) ((N-fluorobenzoyl)-diaminopropionic acid).
3. A compound according to claim 2 wherein Z is selected from Nal, Dap(FB) or AMS(FB) (an oxime of aminooxy serine and 4-fluorobenzaldehyde).
4. A compound according to any of claims 1 to 3 wherein B is selected from Arg, Orn, D-Orn, Cit and His, or N-substituted derivatives thereof.
5. A compound according to any preceding claim wherein B is N .alpha.-substituted with a Me group.
6. A compound according to any of claims 2 to 5 wherein B is Orn or D-Orn, the ornithine residue being substituted at N .delta. with one or two groups selected from fluolobenzoyl (FB), fluoropropionyl (FP), acetyl (Ac), amido (Am), Me, 1-naphthylmethyl (N1), 2-naphthylmethyl (N2), benzyl (Bz) and acyl spacer moieties, wherein the acyl spacer moiety is an acyl group containing a chain of 1-14 carbons, optionally interrupted by heteroatoms, and having a nucleophilic functional group at its end distal to the ornithine N .delta..
7. A compound according to claim 6 wherein the acyl spacer moiety is selected from aminohexanoyl (Ahx), triethyleneglycolamino acyl (TGAS), (Ahx)2, (Ahx)3, (TGAS)2 and (TGAS)3.
8. A compound according to claim 6 wherein B is D-Orn substituted at N .alpha.
with a Me group.
with a Me group.
9. A compound according to claim 6 wherein B is Orn substituted at N .delta.
with FB, FP, Ac, Am, N1, N2, Me and N1, Me and N2, Bz, Bz and FB, Bz and FP, Me and FB, Me and FP, or Me.
with FB, FP, Ac, Am, N1, N2, Me and N1, Me and N2, Bz, Bz and FB, Bz and FP, Me and FB, Me and FP, or Me.
10. A compound according to claim 6 wherein B is D-Orn substituted at N
.delta. with FB, FP, Me and FB, or Me and FP, and optionally substituted at N .alpha. with a Me group.
.delta. with FB, FP, Me and FB, or Me and FP, and optionally substituted at N .alpha. with a Me group.
11. A compound according to any of claim 1 to 5, wherein the cyclic oligopeptide moiety has the sequence: cyclo[D-Tyr - B - Arg - Z - X], wherein B, Z and X are as defined in claim 2, provided that not more than one of the residues in the said sequence may be N .alpha.-methylated.
12. A compound according to claim 11, wherein B is Arg.
13. A compound according to any of claim 1 to 4, wherein the cyclic oligopeptide moiety has the sequence: cyclo[D-Tyr/(Me)D-Tyr - B - Arg/(Me)Arg - Z - X], wherein Z
and X are as defined in claim 2 and wherein B is selected from Arg, (Me)Arg, Orn, Cit, Orn(FB), Orn(FP), Orn(Ac), Orn(Am), Orn(N1), Orn(N2), Orn(Me, N1), Orn(Me, N2), Orn(Me), Orn(Bz), Orn(Bz,FB), Orn(Ahx), Orn(Ahx2), Orn(Ahx3), Orn(TGAS), Orn(TGAS2), Orn(TGAS3), Orn(Me,FB), D-Orn(FB), (Me)D-Orn(FB), (Me)D-Orn(Me,FB), His and Phe, provided that not more than one of the residues in the said sequence may be N.alpha.-methylated.
and X are as defined in claim 2 and wherein B is selected from Arg, (Me)Arg, Orn, Cit, Orn(FB), Orn(FP), Orn(Ac), Orn(Am), Orn(N1), Orn(N2), Orn(Me, N1), Orn(Me, N2), Orn(Me), Orn(Bz), Orn(Bz,FB), Orn(Ahx), Orn(Ahx2), Orn(Ahx3), Orn(TGAS), Orn(TGAS2), Orn(TGAS3), Orn(Me,FB), D-Orn(FB), (Me)D-Orn(FB), (Me)D-Orn(Me,FB), His and Phe, provided that not more than one of the residues in the said sequence may be N.alpha.-methylated.
14. A compound according to claim 13, wherein the first residue is D-Tyr.
15. A compound according to claim 13 or claim 14, wherein the third residue is Arg.
16. A compound according to any of claims 11 to 14, wherein Z is Nal.
17. A compound according to any of claims 11 to 15, wherein X is Gly.
18. A compound according to any of claims 1 to 4, wherein the cyclic oligopeptide moiety has a sequence selected from cvclo[D-Tyr - Arg - Arg - Nal - Gly]
cyclo[D-Tyr - (Me)Arg - Arg - Nal - Gly]
cyclo[D-Tyr - Arg - (Me)Arg - Nal - Gly]
cyclo[D-Tyr - Arg - Arg - Nal - (Me)Gly]
cyclo[D-Tyr - Orn - Arg - Nal - Gly]
cyclo[D-Tyr - Cit - Arg - Nal - Gly]
cyclo[D-Tyr - Arg - Arg - Nal -Ala - Gly]
cyclo[D-Tyr - Arg - Arg - Nal -Ala - Ala]
cyclo[D-Tyr - (Me)Arg - Arg - Nal - (Me)Gly]
cyclo[D-Tyr - (Me)Arg - Arg - (Me)Nal -Gly]
cyclo[(Me)D-Tyr - Arg - Arg - Nal -Ala - Gly]
cyclo[(Me)D-Tyr - Arg - Arg - Nal - Gly]
cyclo[D-Tyr - Orn(FB)- Arg - Nal - Gly]
cyclo[D-Tyr - Orn(FP) - Arg - Nal - Gly]
cyclo[D-Tyr - Orn(Ac) - Arg - Nal - Gly]
cyclo[D-Tyr - Orn(Am) - Arg - Nal - Gly]
cyclo[D-Tyr - Arg - Arg - Nal - Dap(FP)]
cyclo[D-Tyr - Orn(N1) - Arg - Nal - Gly]
cyclo[D-Tyr - Orn(N2) - Arg - Nal - Gly]
cyclo[D-Tyr - Orn(Me,N1) - Arg - Nal - Gly]
cyclo[D-Tyr - Orn(Me,N2) - Arg - Nal - Gly]
cyclo[D-Tyr - Orn(Me) - Arg - Nal - Gly]
cyclo[D-Tyr - Orn(Bz) - Arg - Nal - Gly]
cyclo[D-Tyr - Orn(Bz,FB) - Arg - Nal - Gly]
cyclo[D-Tyr - Orn(Ahx) - Arg - Nal - Gly]
cyclo[D-Tyr - Orn(Ahx3) - Arg - Nal - Gly]
cyclo[D-Tyr - Orn(TGAS) - Arg - Nal - Gly]
cyclo[D-Tyr - Orn(TGAS2) - Arg - Nal - Gly]
cyclo[D-Tyr - Orn(TGAS3) - Arg - Nal - Gly]
cyclo[D-Tyr - Orn(Me,FB)- Arg - Nal - Gly]
cyclo[D-Tyr - D-Orn(FB) - Arg - Nal - Gly]
cyclo[D-Tyr - (Me)D-Orn(FB) - Arg - Nal - Gly]
cyclo[D-Tyr - (Me)D-Orn(Me,FB) - Arg - Nal - Gly]
cyclo[D-Tyr - His - Arg - Nal - Gly]
cyclo[D-Tyr - Phe - Arg - Nal - Gly]
cyclo[D-Tyr - (Me)Arg - Arg - Nal - Gly]
cyclo[D-Tyr - Arg - (Me)Arg - Nal - Gly]
cyclo[D-Tyr - Arg - Arg - Nal - (Me)Gly]
cyclo[D-Tyr - Orn - Arg - Nal - Gly]
cyclo[D-Tyr - Cit - Arg - Nal - Gly]
cyclo[D-Tyr - Arg - Arg - Nal -Ala - Gly]
cyclo[D-Tyr - Arg - Arg - Nal -Ala - Ala]
cyclo[D-Tyr - (Me)Arg - Arg - Nal - (Me)Gly]
cyclo[D-Tyr - (Me)Arg - Arg - (Me)Nal -Gly]
cyclo[(Me)D-Tyr - Arg - Arg - Nal -Ala - Gly]
cyclo[(Me)D-Tyr - Arg - Arg - Nal - Gly]
cyclo[D-Tyr - Orn(FB)- Arg - Nal - Gly]
cyclo[D-Tyr - Orn(FP) - Arg - Nal - Gly]
cyclo[D-Tyr - Orn(Ac) - Arg - Nal - Gly]
cyclo[D-Tyr - Orn(Am) - Arg - Nal - Gly]
cyclo[D-Tyr - Arg - Arg - Nal - Dap(FP)]
cyclo[D-Tyr - Orn(N1) - Arg - Nal - Gly]
cyclo[D-Tyr - Orn(N2) - Arg - Nal - Gly]
cyclo[D-Tyr - Orn(Me,N1) - Arg - Nal - Gly]
cyclo[D-Tyr - Orn(Me,N2) - Arg - Nal - Gly]
cyclo[D-Tyr - Orn(Me) - Arg - Nal - Gly]
cyclo[D-Tyr - Orn(Bz) - Arg - Nal - Gly]
cyclo[D-Tyr - Orn(Bz,FB) - Arg - Nal - Gly]
cyclo[D-Tyr - Orn(Ahx) - Arg - Nal - Gly]
cyclo[D-Tyr - Orn(Ahx3) - Arg - Nal - Gly]
cyclo[D-Tyr - Orn(TGAS) - Arg - Nal - Gly]
cyclo[D-Tyr - Orn(TGAS2) - Arg - Nal - Gly]
cyclo[D-Tyr - Orn(TGAS3) - Arg - Nal - Gly]
cyclo[D-Tyr - Orn(Me,FB)- Arg - Nal - Gly]
cyclo[D-Tyr - D-Orn(FB) - Arg - Nal - Gly]
cyclo[D-Tyr - (Me)D-Orn(FB) - Arg - Nal - Gly]
cyclo[D-Tyr - (Me)D-Orn(Me,FB) - Arg - Nal - Gly]
cyclo[D-Tyr - His - Arg - Nal - Gly]
cyclo[D-Tyr - Phe - Arg - Nal - Gly]
19. A compound according to claim 18 wherein the cyclic oligopeptide moiety has a sequence selected from cyclo[D-Tyr - Arg - Arg - Nal - Gly]
cyclo[D-Tyr - (Me)Arg - Arg - Nal - Gly]
cyclo[D-Tyr - Arg - (Me)Arg - Nal - Gly]
cyclo[D-Tyr - Orn - Arg - Nal - Gly]
cyclo[D-Tyr - Cit - Arg - Nal - Gly]
cyclo[D-Tyr - Orn(FB)- Arg - Nal - Gly]
cyclo[D-Tyr - Orn(FP) - Arg - Nal - Gly]
cyclo[D-Tyr - Orn(Ac) - Arg - Nal - Gly]
cyclo[D-Tyr - Orn(Arn) - Arg -Nal - Gly]
cyclo[D-Tyr - Orn(N1) - Arg - Nal - Gly]
cyclo[D-Tyr - Orn(N2) - Arg - Nal - Gly]
cyclo[D-Tyr - Orn(Me,N1) - Arg - Nal - Gly]
cyclo[D-Tyr - Orn(Me,N2) - Arg - Nal - Gly]
cyclo[D-Tyr - (Me)D-Orn(FB) - Arg - Nal - Gly]
cyclo[D-Tyr - His - Arg - Nal - Gly]
cyclo[D-Tyr - (Me)Arg - Arg - Nal - Gly]
cyclo[D-Tyr - Arg - (Me)Arg - Nal - Gly]
cyclo[D-Tyr - Orn - Arg - Nal - Gly]
cyclo[D-Tyr - Cit - Arg - Nal - Gly]
cyclo[D-Tyr - Orn(FB)- Arg - Nal - Gly]
cyclo[D-Tyr - Orn(FP) - Arg - Nal - Gly]
cyclo[D-Tyr - Orn(Ac) - Arg - Nal - Gly]
cyclo[D-Tyr - Orn(Arn) - Arg -Nal - Gly]
cyclo[D-Tyr - Orn(N1) - Arg - Nal - Gly]
cyclo[D-Tyr - Orn(N2) - Arg - Nal - Gly]
cyclo[D-Tyr - Orn(Me,N1) - Arg - Nal - Gly]
cyclo[D-Tyr - Orn(Me,N2) - Arg - Nal - Gly]
cyclo[D-Tyr - (Me)D-Orn(FB) - Arg - Nal - Gly]
cyclo[D-Tyr - His - Arg - Nal - Gly]
20. A compound according to claim 19 wherein the cyclic oligopeptide moiety has a sequence selected from cyclo[D-Tyr - Orn - Arg - Nal - Gly]
cyclo[D-Tyr - Orn(FB)- Arg - Nal - Gly]
cyclo[D-Tyr - (Me)D-Orn(FB) - Arg - Nal - Gly]
cyclo[D-Tyr - Orn(FB)- Arg - Nal - Gly]
cyclo[D-Tyr - (Me)D-Orn(FB) - Arg - Nal - Gly]
21. A compound according to any preceding claim, wherein the ligand consists of the cyclic oligopeptide moiety.
22. A compound according to any preceding claim, wherein the label is a radiolabel.
23. A compound according to claim 22, wherein the compound contains one or more Dap(FB), Dap(FP), FB or FP groups and one of the fluorine substituents is 18F.
24. A compound according to claim 23 wherein the 18F is present on an FB or FP
substituent at N.delta. of Orn or D-Orn.
substituent at N.delta. of Orn or D-Orn.
25. A compound according to claim 22, having a radiolabel selected from 18F, 47Sc, 51Cr, 52Fe, 52Mm, 56Ni, 57Ni, 62Cu, 64Cu, 67Ga, 68Ga, 72As, 75Br, 76Br, 77Br, 82 Br, 89Zr, 94m Tc, 97Ru, 99m Tc, 111In, 123I, 124I, 125I, 131I, 191Pt, 197Hg, 201T1, 203Pb, 110m In, 120I.
26. A compound according to claim 22 having a radiolabel which is attached to the ligand by means of a complex between an organic complexation agent and a radionuclide, the complex being attached to the ligand in such a way as not to destroy its binding properties to the CXCR4 receptor.
27. A compound according to claim 26, wherein the complexation agent is attached to the ligand by means of a spacer group.
28. A compound according to claim 22, wherein the radiolabel is selected from 32P, 67Cu, 77As, 90Y, 99Mo, 103Ru, 105Ph, 109Pd, 111Ag, 114m In, 117m Sn, 121Sn, 127Te, 131I, 140La, 140Nd, 142Pr, 143Pr, 149Tb, 149Pm, 151Pm, 153Sm, 159Gd, 161Tb, 166Ho, 166Dy, 169Er, 169Yb, 172Tm,175Yb, 177Lu, 186Re, 188Re, 198Au, 199Au, 211At, 211Bi, 212Bi, 213Bi , 225Ac.
29. A compound according to claim 22, wherein the radiolabel is selected from 90Y, 188Re and 1311.
30. A compound, or a pharmaceutically acceptable salt or ester thereof, comprising a cytotoxic moiety and a ligand for the chemokine receptor CXCR4, the ligand having a binding affinity for the CXCR4 receptor, measured as IC50 in the presence of CPCR4, of 250nM or lower, wherein the ligand comprises a cyclic oligopeptide moiety having the motif B-Arg or B-(Me)Arg within the cyclic moiety, and wherein B
is a basic amino acid, a derivative thereof, or phenylalanine, provided that the motif is B-Arg when B is a N.alpha.-methyl derivative of a basic amino acid.
is a basic amino acid, a derivative thereof, or phenylalanine, provided that the motif is B-Arg when B is a N.alpha.-methyl derivative of a basic amino acid.
31. A compound according to claim 30, wherein the cyclic oligopeptide moiety has the sequence:
cyclo[D-Tyr/(Me)D-Tyr - B - Arg/(Me)Arg - Z-(Ala)n - X]
wherein:
B is a basic amino acid, a derivative thereof, or phenylalanine, provided that the motif is B-Arg when B is a N.alpha.-methyl derivative of a basic amino acid, or a pharmaceutically acceptable salt or ester thereof, Z is an amino acid containing an aromatic group in its side chain;
n is I or 0, provided that n is 1 only when the preceding four amino acids in the cyclic moiety sequence are D-Tyr/(Me)D-Tyr-Arg-Arg-Nal; and X is selected from Gly, (Me)Gly, Ala, Dap (diaminopropionic acid), Dap(FP) ((N-fluoropropionyl)-diaminopropionic acid), Dab (diaminobutyric acid), Dab(FP) ((N-fluoropropionyl)-diaminobutyric acid), Dab(FB) ((N-fluorobenzoyl)-diaminobutyric acid) and Dap(FB) ((N-fluorobenzoyl)-diaminopropionic acid).
cyclo[D-Tyr/(Me)D-Tyr - B - Arg/(Me)Arg - Z-(Ala)n - X]
wherein:
B is a basic amino acid, a derivative thereof, or phenylalanine, provided that the motif is B-Arg when B is a N.alpha.-methyl derivative of a basic amino acid, or a pharmaceutically acceptable salt or ester thereof, Z is an amino acid containing an aromatic group in its side chain;
n is I or 0, provided that n is 1 only when the preceding four amino acids in the cyclic moiety sequence are D-Tyr/(Me)D-Tyr-Arg-Arg-Nal; and X is selected from Gly, (Me)Gly, Ala, Dap (diaminopropionic acid), Dap(FP) ((N-fluoropropionyl)-diaminopropionic acid), Dab (diaminobutyric acid), Dab(FP) ((N-fluoropropionyl)-diaminobutyric acid), Dab(FB) ((N-fluorobenzoyl)-diaminobutyric acid) and Dap(FB) ((N-fluorobenzoyl)-diaminopropionic acid).
32. A compound according to claim 31 wherein Z is selected from Nal (L-3-(2-naphthyl)alanine), Dap(FB) or AMS(FB).
33. A compound, or a pharmaceutically acceptable salt or ester thereof, comprising a ligand for the chemokine receptor CXCR4, the ligand having a binding affinity for the CXCR4 receptor, measured as IC50 in the presence of 125I-CPCR4, of 250nM or lower, wherein the ligand comprises a cyclic oligopeptide moiety having the motif B-Arg or B-(Me)Arg within the cyclic moiety, and wherein B is a basic amino acid, a derivative thereof, or phenylalanine, provided that the motif is B-Arg when B
is a N.alpha.-methyl derivative of a basic amino acid, and provided that the oligopeptide moiety does not have the sequence cyclo[D-Tyr - Arg - Arg - Nal - Gly], nor the sequence cyclo[D-Tyr - Orn - Arg - Nal - Gly].
is a N.alpha.-methyl derivative of a basic amino acid, and provided that the oligopeptide moiety does not have the sequence cyclo[D-Tyr - Arg - Arg - Nal - Gly], nor the sequence cyclo[D-Tyr - Orn - Arg - Nal - Gly].
34. A compound according to claim 33, the ligand comprising a cyclic oligopeptide moiety having the sequence:
cyclo[D-Tyr/(Me)D-Tyr - B - Arg/(Me)Arg - Z - (Ala)n - X]
wherein:
B is as defined in claim 33;
Z is an amino acid containing an aromatic group in its side chain;
n is 1 or 0, provided that n is 1 only when the preceding four amino acids in the cyclic moiety sequence are D-Tyr/(Me)D-Tyr-Arg-Arg-Nal; and X is selected from Gly, (Me)Gly, Ala, Dap (diaminopropionic acid), Dap(FP) ((N-fluoropropionyl)-diaminopropionic acid), Dab (diaminobutyric acid), Dab(FP) ((N-fluoropropionyl)-diaminobutyric acid), Dab(FB) ((N-fluorobenzoyl)-diaminobutyric acid) and Dap(FB) ((N-fluorobenzoyl)-diaminopropionic acid).
cyclo[D-Tyr/(Me)D-Tyr - B - Arg/(Me)Arg - Z - (Ala)n - X]
wherein:
B is as defined in claim 33;
Z is an amino acid containing an aromatic group in its side chain;
n is 1 or 0, provided that n is 1 only when the preceding four amino acids in the cyclic moiety sequence are D-Tyr/(Me)D-Tyr-Arg-Arg-Nal; and X is selected from Gly, (Me)Gly, Ala, Dap (diaminopropionic acid), Dap(FP) ((N-fluoropropionyl)-diaminopropionic acid), Dab (diaminobutyric acid), Dab(FP) ((N-fluoropropionyl)-diaminobutyric acid), Dab(FB) ((N-fluorobenzoyl)-diaminobutyric acid) and Dap(FB) ((N-fluorobenzoyl)-diaminopropionic acid).
35. A compound according to claim 34 wherein Z is selected from Nal (L-3-(2-naphthyl)alanine), Dap(FB) or AMS(FB).
36. A compound according to any preceding claim which has been modified by the attachment of one or more hydrophilic moieties.
37. A pharmaceutical composition comprising a compound according to any preceding claim, together with one or more pharmaceutically acceptable excipients.
38. A composition according to claim 37 suitable for injection.
39. A method of synthesis of a compound according to claim 1, the method comprising treating the ligand with a source of a radionuclide under conditions such that the radionuclide, or a complex between an organic complexation agent and the radionuclide, becomes attached to the ligand.
40. A compound according to any of claims 1 to 36, for use in therapy or diaposis.
41. Use of a compound according to any of claims 1 to 36 in the preparation of a medicament for the treatment of a neoplastic condition.
42. Use of a compound according to any of claims 1 to 29 in the preparation of a medicament for the diagnostic imaging of a neoplastic condition.
43. Use according to claim 41 or claim 42 wherein the neoplasia has, or is suspected of having, metastatic potential.
44. Use according to any of claims 41 to 43 wherein the neoplastic condition is breast or prostate cancer.
45. A method of imaging neoplastic tissue, the method comprising the administration, to a subject having or suspected of having a neoplasia, of a compound according to any of claims 1 to 29, and the detection of the compound following distribution thereof in vivo.
46. A method according to claim 45 including the further step, following the detection step, of generating an image of the detected compound.
47. A method of determining the metastatic potential of cells of a neoplasia, the method comprising exposing the cells to a compound according to any of claims 1 to 29, so as to allow the compound to bind to CXCR4 receptors on the surface of the cells, removing unbound compound from the vicinity of the cells, and determining the presence and/or amount of compound bound to the cells.
48. A method according to claim 47 wherein the cells are removed from the neoplasia and exposed to the compound in vitro.
49. A method according to any of claims 45 to 47 wherein the imaging, or determination of the presence and/or amount of bound compound, is performed using PET or SPECT
when the label comprises a radionuclide.
when the label comprises a radionuclide.
50 50. A method of treatment of a neoplastic condition in a subject, the neoplasia having, or being suspected of having, metastatic potential, the method comprising the administration to the subject of a compound according to any of claims 1 to 36.
51. A method according to any of claims 45 to 50 wherein the neoplastic condition is breast or prostate cancer.
52. A method of synthesis of a compound according to any of claims 1 to 29, the method comprising treating the ligand with a source of the detectable label under conditions such that the detectable label, or a complex between an organic complexation agent and the label, becomes bound to the ligand.
53. A method of synthesis of a compound according any of claims 30 to 32, the method comprising treating the ligand with a source of the cytotoxic moiety under conditions such that the cytotoxic moiety becomes bound, directly or indirectly, to the ligand.
54. A compound, or a pharmaceutically acceptable salt or ester thereof, comprising a ligand for the chemokine receptor CXCR4, wherein the ligand comprises a cyclic oligopeptide moiety having the sequence:
cyclo[D-Tyr/(Me)D-Tyr - B - Arg/(Me)Arg - Z-(Ala)n - X]
wherein:
B is as defined in claim 1;
Z is an amino acid containing an aromatic group in its side chain;
n is 1 or 0; and X is selected from Gly, (Me)Gly, Ala, Dap (diaminopropionic acid), Dap(FP) ((N-fluoropropionyl)-diaminopropionic acid), Dab (diaminobutyric acid), Dab(FP) ((N-fluoropropionyl)-diaminobutyric acid), Dab(FB) ((N-fluorobenzoyl)-diaminobutyric acid) and Dap(FB) ((N-fluorobenzoyl)-diaminopropionic acid), the compound optionally comprising a detectable label, provided that, when the compound does not comprise a detectable label, the cyclic oligopeptide moiety does not have the sequence cyclo[D-Tyr - Arg - Arg - Nal - Gly], nor the sequence cyclo[D-Tyr - Orn - Arg - Nal -Gly].
cyclo[D-Tyr/(Me)D-Tyr - B - Arg/(Me)Arg - Z-(Ala)n - X]
wherein:
B is as defined in claim 1;
Z is an amino acid containing an aromatic group in its side chain;
n is 1 or 0; and X is selected from Gly, (Me)Gly, Ala, Dap (diaminopropionic acid), Dap(FP) ((N-fluoropropionyl)-diaminopropionic acid), Dab (diaminobutyric acid), Dab(FP) ((N-fluoropropionyl)-diaminobutyric acid), Dab(FB) ((N-fluorobenzoyl)-diaminobutyric acid) and Dap(FB) ((N-fluorobenzoyl)-diaminopropionic acid), the compound optionally comprising a detectable label, provided that, when the compound does not comprise a detectable label, the cyclic oligopeptide moiety does not have the sequence cyclo[D-Tyr - Arg - Arg - Nal - Gly], nor the sequence cyclo[D-Tyr - Orn - Arg - Nal -Gly].
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB0603901.0 | 2006-02-27 | ||
| GB0603901A GB0603901D0 (en) | 2006-02-27 | 2006-02-27 | Cancer imaging and treatment |
| GB0610962A GB0610962D0 (en) | 2006-06-02 | 2006-06-02 | Cancer imaging and treatment |
| GB0610962.3 | 2006-06-02 | ||
| PCT/GB2007/000684 WO2007096662A2 (en) | 2006-02-27 | 2007-02-27 | Cancer imaging and treatment |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2643744A1 true CA2643744A1 (en) | 2007-08-30 |
Family
ID=37963490
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002643744A Abandoned CA2643744A1 (en) | 2006-02-27 | 2007-02-27 | Cancer imaging and treatment |
Country Status (6)
| Country | Link |
|---|---|
| US (2) | US8628750B2 (en) |
| EP (1) | EP1991562A2 (en) |
| JP (2) | JP5308829B2 (en) |
| KR (1) | KR20090041360A (en) |
| CA (1) | CA2643744A1 (en) |
| WO (1) | WO2007096662A2 (en) |
Families Citing this family (35)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2643744A1 (en) * | 2006-02-27 | 2007-08-30 | Technische Universitaet Muenchen | Cancer imaging and treatment |
| JO2776B1 (en) | 2007-05-30 | 2014-03-15 | ايلي ليلي اند كومباني | Cyclic Peptide CXCR4 Antagonists |
| GB0716897D0 (en) | 2007-08-30 | 2007-10-10 | Univ Muenchen Tech | Cancer imaging and treatment |
| WO2010053572A2 (en) | 2008-11-07 | 2010-05-14 | Massachusetts Institute Of Technology | Aminoalcohol lipidoids and uses thereof |
| EP2380596A1 (en) * | 2010-04-20 | 2011-10-26 | Technische Universität München | Cyclopentapeptide derivatives and uses thereof |
| EP2380597A1 (en) * | 2010-04-20 | 2011-10-26 | Technische Universität München | Cyclopeptide derivatives and uses thereof |
| JP6145404B2 (en) * | 2010-05-07 | 2017-06-14 | エフ・ホフマン−ラ・ロシュ・アクチェンゲゼルシャフト | Diagnostic methods for ex vivo cell detection |
| KR101306157B1 (en) * | 2010-09-10 | 2013-09-10 | 연세대학교 산학협력단 | Compositions for Preventing or Treating Tumors Comprising Cyclopentapeptides |
| CA2831392C (en) | 2011-03-28 | 2020-04-28 | Massachusetts Institute Of Technology | Conjugated lipomers and uses thereof |
| PE20181541A1 (en) | 2011-10-27 | 2018-09-26 | Massachusetts Inst Technology | DERIVATIVES OF AMINO ACIDS FUNCTIONALIZED IN THE N TERMINAL, CAPABLE OF FORMING DRUG ENCAPSULATING MICROSPHERES |
| ES2647076T3 (en) * | 2012-06-06 | 2017-12-19 | Polyphor Ag | Beta fork peptidomimetics |
| WO2014028487A1 (en) | 2012-08-13 | 2014-02-20 | Massachusetts Institute Of Technology | Amine-containing lipidoids and uses thereof |
| HRP20191254T1 (en) | 2014-05-21 | 2019-10-18 | Entrada Therapeutics, Inc. | PEPTIDES INPETING CELLS AND PROCEDURES FOR THEIR PRODUCTION AND USE |
| US10815276B2 (en) | 2014-05-21 | 2020-10-27 | Entrada Therapeutics, Inc. | Cell penetrating peptides and methods of making and using thereof |
| EP3587409B8 (en) | 2014-05-30 | 2022-07-13 | Translate Bio, Inc. | Biodegradable lipids for delivery of nucleic acids |
| CN106573959B (en) | 2014-06-06 | 2022-03-25 | 慕尼黑工业大学 | Modified cyclic pentapeptides and uses thereof |
| KR102511554B1 (en) | 2014-06-24 | 2023-03-16 | 샤이어 휴먼 지네틱 테라피즈 인크. | Stereochemically enriched compositions for delivery of nucleic acids |
| WO2016004202A1 (en) | 2014-07-02 | 2016-01-07 | Massachusetts Institute Of Technology | Polyamine-fatty acid derived lipidoids and uses thereof |
| EP3185880B1 (en) | 2014-08-27 | 2020-02-12 | Ohio State Innovation Foundation | Improved peptidyl calcineurin inhibitors |
| LT3310764T (en) | 2015-06-19 | 2023-06-12 | Massachusetts Institute Of Technology | Alkenyl substituted 2,5-piperazinediones and their use in compositions for delivering an agent to a subject or cell |
| US9890187B2 (en) | 2015-06-26 | 2018-02-13 | Epos-Iasis Research And Development, Ltd. | Prototype systems of theranostic biomarkers for in vivo molecular management of cancer |
| EP3509612A4 (en) * | 2016-09-06 | 2021-07-21 | Mainline Biosciences | Cxcr4 antagonists and methods of use |
| WO2019050564A1 (en) * | 2017-09-05 | 2019-03-14 | Mainline Biosciences | High affinity cxcr4 selective binding conjugate and method for using the same |
| US10639379B2 (en) * | 2017-09-05 | 2020-05-05 | Mainline Biosciences Llc | High affinity CXCR4 selective binding conjugate and method for using the same |
| US11123437B2 (en) | 2017-09-05 | 2021-09-21 | Mainline Biosciences, Inc. | Selective CXCR4 binding peptide conjugate and methods for making and using the same |
| WO2019070962A1 (en) | 2017-10-04 | 2019-04-11 | Ohio State Innovation Foundation | Bicyclic peptidyl inhibitors |
| WO2019148194A2 (en) | 2018-01-29 | 2019-08-01 | Ohio State Innovation Foundation | Peptidyl inhibitors of calcineurin-nfat interaction |
| US11793884B2 (en) | 2018-01-29 | 2023-10-24 | Ohio State Innovation Foundation | Cyclic peptidyl inhibitors of CAL-PDZ binding domain |
| WO2019165183A1 (en) | 2018-02-22 | 2019-08-29 | Entrada Therapeutics, Inc. | Compositions and methods for treating mitochondrial neurogastrointestinal encephalopathy |
| EP3790890A4 (en) | 2018-05-09 | 2022-03-02 | Ohio State Innovation Foundation | CYCLIC, CELL-PENETRATING PEPTIDES WITH ONE OR MORE HYDROPHOBIC RAILS |
| WO2020053255A1 (en) | 2018-09-12 | 2020-03-19 | Technische Universität München | Therapeutic and diagnostic agents for cancer |
| CA3108450A1 (en) | 2018-09-12 | 2020-03-19 | Technische Universitat Munchen | Cxcr4-targeted diagnostic and therapeutic agents with reduced species selectivity |
| WO2021150258A1 (en) * | 2020-01-26 | 2021-07-29 | Mainline Biosciences Llc | Isotopically labelled selective cxcr4 binding peptide conjugate and methods for making and using the same |
| EP4043041A1 (en) | 2021-02-15 | 2022-08-17 | Technische Universität München | Cxcr4-ligands for diagnostic and therapeutic use and precursors thereof |
| WO2024259228A1 (en) * | 2023-06-16 | 2024-12-19 | Prime Medicine, Inc. | Cyclic peptide lipids for nanoparticle formulations |
Family Cites Families (15)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE4444260A1 (en) * | 1994-12-13 | 1996-06-20 | Hoechst Ag | Cyclohexapeptides and their mixtures, process for their preparation and their use |
| WO1999040947A2 (en) * | 1998-02-11 | 1999-08-19 | Resolution Pharmaceuticals Inc. | Angiogenesis targeting molecules |
| PL350998A1 (en) | 1999-03-24 | 2003-02-24 | Anormed Inc | Chemokine recpetor binding heterocyclic compounds |
| US6319675B1 (en) | 1999-11-24 | 2001-11-20 | Millennium Pharmaceuticals, Inc. | Methods for detecting and/or identifying agents which bind and/or modulate function of “bonzo” chemokine receptor |
| ES2747357T3 (en) | 2001-03-14 | 2020-03-10 | Dako Denmark As | MHC molecule constructs and their uses for diagnosis and therapy |
| WO2003066830A2 (en) | 2002-02-08 | 2003-08-14 | Genetastix Corporation | Human monoclonal antibodies against membrane proteins |
| US20040009149A1 (en) * | 2002-02-27 | 2004-01-15 | Altman John D. | Multimeric binding complexes |
| AU2003261723A1 (en) | 2002-08-27 | 2004-03-19 | Takeda Chemical Industries, Ltd. | Cxcr4 antagonist and use thereof |
| JP4391123B2 (en) * | 2002-10-24 | 2009-12-24 | 株式会社オーファンリンク | Novel CXCR4 antagonist |
| JP2006524242A (en) | 2003-03-27 | 2006-10-26 | エモリー ユニバーシティー | CXCR4 antagonists and methods of their use |
| EP1620567A1 (en) | 2003-04-15 | 2006-02-01 | Hans-Jürgen Thiesen | Method for diagnosing rheumatoid arthritis or osteoarthritis |
| WO2004094465A2 (en) | 2003-04-23 | 2004-11-04 | The Board Of Trustees Of The University Of Illinois Office Of Technology Management University Of Illinois At Urbana-Champaign | Synthetic molecules that mimic chemokines |
| NO20035681D0 (en) * | 2003-12-18 | 2003-12-18 | Amersham Health As | Optical imaging of lung cancer |
| CA2643744A1 (en) * | 2006-02-27 | 2007-08-30 | Technische Universitaet Muenchen | Cancer imaging and treatment |
| GB0716897D0 (en) * | 2007-08-30 | 2007-10-10 | Univ Muenchen Tech | Cancer imaging and treatment |
-
2007
- 2007-02-27 CA CA002643744A patent/CA2643744A1/en not_active Abandoned
- 2007-02-27 JP JP2008555880A patent/JP5308829B2/en not_active Expired - Fee Related
- 2007-02-27 EP EP07712802A patent/EP1991562A2/en not_active Withdrawn
- 2007-02-27 US US12/280,829 patent/US8628750B2/en not_active Expired - Fee Related
- 2007-02-27 WO PCT/GB2007/000684 patent/WO2007096662A2/en not_active Ceased
- 2007-02-27 KR KR1020087020905A patent/KR20090041360A/en not_active Withdrawn
-
2013
- 2013-03-29 JP JP2013071288A patent/JP5676673B2/en not_active Expired - Fee Related
- 2013-12-12 US US14/104,476 patent/US20140100172A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| WO2007096662A3 (en) | 2008-02-14 |
| US8628750B2 (en) | 2014-01-14 |
| WO2007096662A2 (en) | 2007-08-30 |
| US20140100172A1 (en) | 2014-04-10 |
| EP1991562A2 (en) | 2008-11-19 |
| JP2013129676A (en) | 2013-07-04 |
| WO2007096662A9 (en) | 2008-10-30 |
| JP5676673B2 (en) | 2015-02-25 |
| US20110027175A1 (en) | 2011-02-03 |
| JP2009528286A (en) | 2009-08-06 |
| KR20090041360A (en) | 2009-04-28 |
| JP5308829B2 (en) | 2013-10-09 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CA2643744A1 (en) | Cancer imaging and treatment | |
| JP7534498B2 (en) | GRPR Antagonists for the Detection, Diagnosis and Treatment of GRPR-Positive Cancers - Patent application | |
| JP4236282B2 (en) | Radiolabeled peptide composition for site-specific targeting | |
| CA2841238C (en) | Enhanced in vivo targeting of radiolabelled peptides with the means of enzyme inhibitors | |
| EP2380596A1 (en) | Cyclopentapeptide derivatives and uses thereof | |
| Breeman et al. | Optimised labeling, preclinical and initial clinical aspects of CCK-2 receptor-targeting with 3 radiolabeled peptides | |
| CA2807491A1 (en) | F18 c-met binding cyclic peptide radiotracers and compositions thereof | |
| CA3118743A1 (en) | Radiolabeled bombesin-derived compounds for in vivo imaging of gastrin-releasing peptide receptor (grpr) and treatment of grpr-related disorders | |
| CA3178858A1 (en) | Copper-containing theragnostic compounds and methods of use | |
| CA3245281A1 (en) | Compounds targeting SSTR2, their preparation process and their use | |
| NZ522200A (en) | RGD (ARG-GLY-ASP) coupled to (neuro)peptides | |
| Wester et al. | Radiolabeled carbohydrated somatostatin analogs: a review of the current status | |
| CA3204021A1 (en) | Cxcr4-ligands for diagnostic and therapeutic use and precursors thereof | |
| DK2795317T3 (en) | Composition for use in a cancer selection method | |
| JP2023549469A (en) | Novel CXCR4 target compound | |
| CA2464002C (en) | Pacap compositions and methods for tumor imaging and therapy | |
| CN120981248A (en) | Compound targeting fibroblast activation protein and application thereof | |
| CA3246188A1 (en) | Radiolabeled compounds for in vivo imaging of gastrin-releasing peptide receptor (grpr) and treatment of grpr-related disorders | |
| JP2011527670A (en) | Dicarba analog of octreotide | |
| CN116917278A (en) | Bivalent fibroblast activation protein ligands for targeted delivery applications | |
| TW202231655A (en) | Improved cholecystokinin-2 receptor (cck2r) targeting for diagnosis and therapy | |
| Obeid et al. | Improving GRPR-targeting peptides for radiotheranostics application: insights from chelator modifications and α-methyl-L tryptophan substitution | |
| CA2247430A1 (en) | Use of labelled cck-b receptor ligands for the detection and localization of malignant human tumors | |
| JP2024540169A (en) | Methods for Treating Cancer | |
| JPWO2022082312A5 (en) |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| FZDE | Discontinued |
Effective date: 20161114 |
|
| FZDE | Discontinued |
Effective date: 20161114 |